What do we need GMP compliant facility (R1 billion 2008) Flow, segregation, containment, environmental, statutory Modern technologies for raw material, intermediate and final product testing Invirto, invivo, reduce, refine, replace Commercial validated Elisa kits R5k /100 test Masterseed/ cell analyses +160 strains, Certified Authority R1m/product Strain ID, purity, BVD, Mad cow, Mycoplasms etc Stability/shelflife infrastructure, qualified people, time Containment labs Zoonoses | Onderstepoort Biological Products © |22nd February 2013Page 43

What do we need Achieve higher quality through continual improvement Labour intensive Training/ capable staff Quality Control test research & development Validation Reference material Proficiency testing Equipment- reproducible, Automised or IT controlled maintenance & validation Supplier compliance & audits GMP increase cost | Onderstepoort Biological Products © |22nd February 2013Page 44

What do we need Small animal unit back to compliance HVAC, steam, building management system Specific pathogen free animals Time for breeding Large animals Animal ergonomics Test facility In vivo R&D to move to invitro ISO 17025/ GCP Bio-security | Onderstepoort Biological Products © |22nd February 2013Page 45

Benefits GMP compliance Globalisation and competition Product according client need Product to regulatory compliance (Product, environmental, Bio containment etc.) Sustainability Contract work (production, quality control & clinical work) Reference lab Fulfil expectation Shareholder, customer, employee & supplier Be a global biotech manufacturer | Onderstepoort Biological Products © |22nd February 2013Page 46

R&D and Production | Onderstepoort Biological Products © |22nd February 2013Page 47

R&D and Production Research Development Application Testing Pilot Product positive cash flow negative cash flow 5-10 years several years product life-cycle production R&D Chlamysure vaccine : B-Phemeral vaccine : RVF vaccine Clone 13: 2001 – 2009 Average R&D spend of OBP per annum ( ) R 2 – R 2.5 million, <4% of revenues generated (multinationals able to invest (12-20% in R&D) Cost of new product development: average R7m - R 10m | Onderstepoort Biological Products © |22nd February 2013Page 48

Vaccine Bank/Reserve | Onderstepoort Biological Products © |22nd February 2013Page 49

Vaccine Bank and Reserve Categories of animal vaccines requiring different approaches: generally used vaccines which are driven by commercial imperatives and strategic vaccines which are of vital importance to the country and region in terms of controlling and eliminating diseases (eg AHS, FMD, RVF) (which require and should receive state support) Vaccine Bank and Reserve (contingency vaccines) Reserve: rolling stock Bank: bulk and/or ready to use : to ensure product availability and rapid response in case of threat of outbreaks Vaccines against diseases that can have devastating effect to the economy of the country (in terms of trade, food security and safety) Vaccines for which there is unique expertise in research, development and production, mainly because of their restricted distribution to Africa, or in some cases to South Africa Vaccines against transboundary and other exotic diseases that are a threat to South Africa OBP’s products, as well as other local and international suppliers OBP has already approached by an international organisation to establish a vaccine bank for RVF for Africa | Onderstepoort Biological Products © |22nd February 2013Page 50

Production and related challenges | Onderstepoort Biological Products © |22nd February 2013Page 51

Stages in Vaccine Production Pre-production Cellbank, masterseed and seedstock bank QC tests: sterility, purity, safety, potency and identity Upstream processing Medium preparation, preparation of cells, seedstock of antigen prepared into working seedstock) Up-scaled antigen production Open or closed mammalian cell systems, fermentors Down- stream processing Purification, inactivation, formulation Filling and lyophilisation QC testing and release Sterility, purity, safety, efficacy and identity Final labeling and packaging Transferred to distribution for sale | Onderstepoort Biological Products © |22nd February 2013Page 52 * in-process testing * * *